NOVEL PROPENONE DERIVATIVES CONTAINING

AROMATIC RINGS, A MAUFACTURING PROCESS THEREOF

AND A COMPOSITION CONTAINING THE SAME USING AS

AN ANTIINFLAMMATORY AGENT Technical Field [1] The present invention relates to novel propenone derivatives containing aromatic ring, a manufacturing process thereof and a composition containing the same using as an anti-inflammatory agent. [2] Background Art [3] Inflammation and pain occur as a secondary symptoms associated with direct symptom or infection. There has been found that those are closely correlated with the reproduction of arachidonic acid metabolite therefore much of interests have been focused on their mechanism till now. Where cells are received with some stimulus phospholipase, especially PLA (phospholipase A ) present in various cells or tissues such as cellular membrane, granule, secreted fluid etc in all bacteria and animals, hydrolyzes ester linked fatty acid with sn-2 position of glycero-phospholipid located in cellular membrane to produce unsaturated fatty acid and lysophospholipid. In particular, it has been reported PLA2 enzyme to act on the release of ester type arachidonic acid (A. A) bound to 2 position of cellular membrane phospholipid as an rate determining enzyme and then the A.A is metabolized to reproduce various eicosanoids such as PGs (prostaglandins), TXs (Thromboxanes), LTs (Leukotrienes) (Murakami M. et al., Reviews in Immunology, 12, pp225-283, 1997; Verheij H. M. et al., Rev. Physiol. Biochem. Pharmacol., 91, pp92-117, 1998). The eicosanoids is reported to show various physiological actions for example, vasodilation activity, vascular permeation activity, bronchial asthma, chemotactic activity to inflammatory cell such as neutrophil, macrophage at al, or anaphylaxis (Lynn W. S. et al., Am. J. Pathol, 96, p663, 1979; Vadas P. et al., Life ScL, 36, pl721, 1980) and to be correlated with various physiological activity such as the mucosal protection in gastro- intestine, the regulation of normal kidney function or reproductive organs (Kam P. C. A. et al., Anaesthesia, 55, pp442-449, 2000; Cellotti F. et al., Pharmacological Research, 43(5). pp429-436, 2001). On the other hand, the released lysophospholipid by PLA2 enzyme is bound to acetyl group at sn-2 position by the action of lyso PAF acetyl reductase enzyme, an inflammatory mediator. [4] The reproduction of PGs and TXs is induced by COXs (Cyclooxygenases) (Urade Y. et al., /. Biol. Chem., 262 p3820, 1987; Urade Y. et al., /. Immunol, ML p2982, 1989) and there are two iso-forms of COXs, i.e., COX-I and COX-2 which show about 70 kDa of M. W. and about 60% similarity in amino acid sequence between each other. [5] The role of COX-I in cells is to reproduce various prostanoids essential in regulating their house keeping activity, for example, the reproduction of platelet induced TXA2, vascular endothelial cells induced anti-thrombogenic prostacycline, renal blood flow regulating prostanoid etc (Kramer, S. A. et al, Arch. Biochem. Biophys., 293. p391, 1992). COX-2 which induces PG production at inflammatory site, is immediately induced by various factors such as pro-inflammatory cytokines, growth factor, LPS (lipo-polysaccharide), phorbol ester, c-AMP-elevated factor, and some G- protein coupled agonist et al (Xie, W et al., Proc. Natl. Acad. ScL USA, 88, p2691, 1991; Fletcher B. S. et al., /. Biol. Chem., 268, p9049, 1993). While the anti¬ inflammatory, analgesic and antipyretic action of world- widely available anti¬ inflammatory drug i.e., NSAIDs (Non-steroidal anti-inflammatory drugs) results from the inhibition of COX-I, the drug gives rise to various adverse action such as gastric disorder etc caused thereby (Seeds M. C. et al., Clinical Reviews in Allergy and Immunology, \J_, pp5-26, 1999). Besides various COXs, various LOXs (lypoxygenase) known as a SRA-A (Slow Reacting Substance of Anaphylaxis) are synthesized from A.A by the action of 5-LOX (5-lipoxygenase) enzyme having about 78kDa of M.W., which are classified into 8-LOX, 12-LOX, 15-LOX etc according to the position of substrate oxidizing residue (Silverman E. S. et al., Proceeding of Association of American Physicians, 116(6). pp525-536, 1999). [6] NO (Nitric oxide) is produced by the conversion from L-arginine to L-citrulline by the action of NOS (Nitric Oxide Synthase) and the NOS is classified into eNOS, nNOS and iNOS (Nathan C, FASEB J., 6, pp3051-3064, 1992). The NO, a gas phase free radical which is induced by the action of iNOS activity caused by the LPS stimulation, an bacterial endotoxin existed in the outer cell membrane of Gram-negative bacteria or various cytokines, relates to various physiological action such as neuronal transmission, blood vessel maintenance, tumor removal etc as well as causes to various diseases for example, septic shock, de-myelination diseases such as oligodendrocyte generation and neuronal degenerative disease, multiple sclerosis (MS) in case of it s overproduction (Nathan C. et al., /. Biol. Chem., 269, ppl3725-13728, 1994; Chen Y. C. et al., Biochemical Pharmacology, ppl821-1832, 2003). Additionally, the other in¬ flammatory cytokines such as TNF-alpha (Tumor Necrosis Factor), IL lbeta (Interleukin I beta) etc are induced thereby. TNF-alpha, principle cytokine, shows various physiological actions such as, fever, shock, macrophage activation, an- giogenesis, bone resorption, cytotocicity to the many cells, polymorph chemotoxin irritation etc. IL 1-beta is also correlated with various inflammatory expression and the mechanism of iNOS mediated by cytokine has been not identified till now. Those in¬ flammatory cytokines such as TNF- alpha and IL 1-beta have been reported to express iNOS through NF-kappa B activation by binding to their binding receptors correlated therewith (Kim Y. M. et al., Nitric oxide, 5£5}, pp504-513, 2001). NF-kappa B remained in inactivated form by binding to protein, activates various MAPKs (Mitogen- activated Protein Kinases) by the signal transduction such as LPS inducement and the activated NF-kappa B by I kappa B alpha dissociation, in¬ corporates into inner nuclear, which regulates various gene expression of iNOS as well as cytokines as a transcription factor (Siebenlist U. et al., Annu. Rev. Cell. Biol, JO, pp405-455, 1994; Lukiw W. J. et al., /. Neurol.sci. Res., 53, pp583-592 1998). [7] [8] Therefore, the present inventors have endeavored to develop novel anti¬ inflammatory agents through modifying the basic structure of Selebrex and syn¬ thesizing aromatic ring comprising propenone derivatives, and have found that they show potent anti-inflammatory activity confirmed by various experiments such as the inhibition test of COX and 5-LOX enzyme activity and the reproduction of TNF-alpha and IL 1-betta. [9] Disclosure of Invention Technical Problem [10] The present invention provides novel aromatic ring comprising propenone derivatives, a manufacturing process thereof and a composition containing the same using as an anti-inflammatory agent. [H] Technical Solution [12] According to one aspect, the present invention provides novel aromatic ring comprising propenone derivatives represented by general formula (I), the pharma¬ ceutically acceptable salt and the isomer thereof: [13] [14] Chemistry Figure 1

[15] (D [16] [17] wherein, [18] A and B are independently five or six member aromatic ring or heterocyclic ring substituted with at least one R"group respectively wherein R"is at least one group selected from a hydrogen atom, halogen atom, C -C lower alkyl group and ketone 1 4 group substituted with C -C lower alkyl group and ketone group substituted with C -C 1 4 1 lower alkyl group; 4 [19] R'is independently at least one group selected from a hydrogen atom, halogen atom, C -C lower alkyl group and ketone group substituted with C -C lower alkyl group. [20] [21] In the above formula (I), preferable A and B rings include benzene, 2-thiopene, 3-thiopene, 2-furan, 3-furan, 2-pyridine and 3-pyridine substituted with R"and preferable R 'or R"group include hydrogen atom, halogen atom, methyl group, ethyl group, methyloxo group and ethyloxo group. [22] According to a preferred embodiment of the aspect invention, there is provided a compound of following general formula (Ia), the pharmaceutically acceptable salt or the isomer thereof: [23] [24] ChemistryFigure 2

[25] (Ia) [26] wherein, [27] P and Q are oxygen atom, sulfur atom or radical of W wherein W is CH=CH or CH=N; R to R is independently at least one group selected from a hydrogen atom, 1 6 halogen atom, C -C lower alkyl group and ketone group substituted with C -C lower alkyl group. [28] [29] In the above formula (Ia), preferable R to R include hydrogen atom, halogen 1 6 atom, methyl group, ethyl group, methyloxo group and ethyloxo group. [30] [31] In preferred embodiment, the most preferred compound is one selected from the group consisting of; [32] 3-phenyl- l-pyridin-2-yl-propenone, 3-furan-2-yl- l-pyridin-2-yl-propenone, 3-furan-3-yl-l-pyridin-2-yl-propenone, l-pyridin-2-yl-3-thiopen-2-yl-propenone, l-pyridin-2-yl-3-thiopen-3-yl-propenone, 3-furan-2-yl-l-pyridin-3-yl-propenone, 3-furan-3-yl-l-pyridin-3-yl-propenone, l-pyridin-3-yl-3-thiopen-3-yl-propenone, 1,3-diphenyl propenone, l-phenyl-3-thiopen-2-yl-propenone, l,3-di-thiopen-2-yl-propenone, 3-thiopen-3-yl-l-thiopen-2-yl-propenone, 3-furan-2-yl-l-thiopen-2-yl-propenone, l,3-di-furan-2-yl-propenone, l-furan-2-yl-3-pyridin-2-yl-propenone, 3-(3-methyl-thiopen-2-yl)- l-pyridin-2-yl-propenone, and l-(5-chloro-thiopen-2-yl)-3-furan-2-yl-propenone. [33] [34] The inventive compounds represented by general formula (I) can be transformed into their pharmaceutically acceptable salt and solvates by the conventional method well known in the art. For the salts, acid-addition salt thereof formed by a pharma¬ ceutically acceptable free acid thereof is useful and can be prepared by the con¬ ventional method. For example, after dissolving the compound in the excess amount of acid solution, the salts are precipitated by the water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile to prepare acid addition salt thereof and further the mixture of equivalent amount of compound and diluted acid with water or alcohol such as glycol monomethylether, can be heated and subsequently dried by evaporation or filtrated under reduced pressure to obtain dried salt form thereof. [35] [36] As a free acid of above-described method, organic acid or inorganic acid can be used. For example, organic acid such as methansulfonic acid, /?-toluensulfonic acid, acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonylic acid, vanillic acid, hydroiodic acid and the like, and inorganic acid such as hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid and the like can be used herein. [37] [38] Further, the pharmaceutically acceptable metal salt form of inventive compounds may be prepared by using base. The alkali metal or alkali-earth metal salt thereof can be prepared by the conventional method, for example, after dissolving the compound in the excess amount of alkali metal hydroxide or alkali-earth metal hydroxide solution, the insoluble salts are filtered and remaining filtrate is subjected to evaporation and drying to obtain the metal salt thereof. As a metal salt of the present invention, sodium, potassium or calcium salt are pharmaceutically suitable and the cor¬ responding silver salt can be prepared by reacting alkali metal salt or alkali-earth metal salt with suitable silver salt such as silver nitrate. [39] [40] The pharmaceutically acceptable salt of the present compound comprise all the acidic or basic salt which may be present at the compounds, if it does not indicated specifically herein. For example, the pharmaceutically acceptable salt of the present invention comprise the salt of hydroxyl group such as the sodium, calcium and potassium salt thereof; the salt of amino group such as the hydrogen bromide salt, sulfuric acid salt, hydrogen sulfuric acid salt, phosphate salt, hydrogen phosphate salt, dihydrophosphate salt, acetate salt, succinate salt, citrate salt, tartarate salt, lactate salt, mandelate salt, methanesulfonate(mesylate) salt and /?-toluenesulfonate (tosylate) salt etc, which can be prepared by the conventional method well known in the art. [41] [42] There may exist in the form of optically different diastereomers since the present compounds have unsymmetrical centers, accordingly, the compounds of the present invention comprise all the optically active isomers, R or S stereoisomers and the mixtures thereof. Present invention also comprises all the uses of racemic mixture, more than one optically active isomer or the mixtures thereof as well as all the preparation or isolation method of the diastereomer well known in the art. [43] [44] The inventive compounds of the present invention may be prepared in accordance with the following preferred embodiment. [45] It is another object of the present invention to provide a method for preparing novel propenone derivatives represented by general chemical formula (I) comprising the steps consisting of: reacting ketone represented by general chemical formula (II) with aldehyde represented by general chemical formula (III) in the presence of strong acid such as potassium hydroxide. [46] ChemistryFigure 3

O

[47] (H) [48] [49] ChemistryFigure 4 [50] (IH) [51] [52] wherein the definitions of A, B, R'and R"are same with those defined in general chemical formula (I). [53] [54] The compounds of the present invention may be chemically synthesized by the methods which will be explained by following reaction schemes hereinafter, which are merely exemplary and in no way limit the invention. The reaction schemes show the steps for preparing the representative compounds of the present invention, and the other compounds also may be produced by following the steps with appropriate modi¬ fications of reagents and starting materials, which are envisaged by those skilled in the art. [55] [56] GENERALSYNTHETICPROCEDURES [57] Scheme 1 [58]

[59] As depicted in above Scheme 1, the propenone compound (I) may be prepared by following step; [60] A ketone represented by general chemical formula (II) is reacted with aldehyde represented by general chemical formula (III) in the presence of strong acid, preferably, potassium hydroxide, sodium hydroxide, more preferably, sodium hydroxide dissolved in solvent mixture mixed with methanol and water in the mixed ratio ranging from 1-8: 1, preferably, 3-5:1. [61] [62] The compound of the present invention show potent anti-inflammatory activity confirmed by various experiments for example, the inhibition test of COX and 5-LOX enzyme activity, the inhibition test of LTC 4 reproduction and NO production, MTT assay test, the inhibition test on the iNOS and COX-2 protein expression and PGE re¬ production using RAW 264.7 macrophage etc therefore we have confirmed that present compounds can be useful in treating and preventing various inflammatory disease. [63] [64] It is another object of the present invention to provide the pharmaceutical composition comprising an efficient amount of the compound represented by general formula (I) and (Ia) or the pharmaceutically acceptable salt thereof as an active ingredient in amount effective to alleviate or treat inflammatory diseases together with pharmaceutically acceptable carriers or diluents. [65] [66] The term "inflammatory disease" disclosed herein comprises all the inflammatory diseases caused by inflammatory action such as gastritis, colitis, rheumatic arthritis, os¬ teoarthritis, joint involved inflammatory disease, nephritis, hepatitis, arteriosclerosis, cancer or degenerative disease and so on. [67] [68] The pharmaceutical composition of the present invention can contain about 0.01 ~ 50 % by weight of the above extract based on the total weight of the composition. [69] [70] The compound of formula (I) according to the present invention can be provided as a pharmaceutical composition containing pharmaceutically acceptable carriers, adjuvants or diluents. For example, the compounds of the present invention can be dissolved in oils, propylene glycol or other solvents which are commonly used to produce an injection. Suitable examples of the carriers include physiological saline, polyethylene glycol, ethanol, vegetable oils, isopropyl myristate, etc., but are not limited to them. For topical administration, the compounds of the present invention can be formulated in the form of ointments and creams. [71] [72] Hereinafter, the following formulation methods and excipients are merely exemplary and in no way limit the invention. [73] [74] The compounds of the present invention in pharmaceutical dosage forms may be used in the form of their pharmaceutically acceptable salts, and also may be used alone or in appropriate association, as well as in combination with other pharmaceutically active compounds. [75] [76] The compounds of the present invention may be formulated into preparations for injections by dissolving, suspending, or emulsifying them in aqueous solvents such as normal saline, 5% Dextrose, or non-aqueous solvent such as vegetable oil, synthetic aliphatic acid glycerides, esters of higher aliphatic acids or propylene glycol. The formulation may include conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifying agents, stabilizers and preservatives. [77] [78] The desirable dose of the inventive compounds varies depending on the condition and the weight of the subject, severity, drug form, route and period of administration, and may be chosen by those skilled in the art. However, in order to obtain desirable effects, it is generally recommended to administer at the amount ranging 0.0001 - 100 mg/kg, preferably 0.001 100 mg/kg by weight/day of the inventive compounds of the present invention. The dose may be administered in single or divided into several times per day. In terms of composition, the compounds should be present between 0.0001 to 10% by weight, preferably 0.0001 to 1% by weight based on the total weight of the composition. [79] [80] The pharmaceutical composition of present invention can be administered to a subject animal such as mammals (rat, mouse, domestic animals or human) via various routes. All modes of administration are contemplated, for example, administration can be made orally, rectally or by intravenous, intramuscular, subcutaneous, intrathecal, epidural or intracerebroventricular injection. [81] [82] It is an object of the present invention to provide a use of a propenone compound represented by general chemical formula (I) or (Ia) for the preparation of therapeutic agent for the treatment and prevention of inflammatory disease activity in mammal or human. [83] [84] It is an object of the present invention to provide a method of treating or preventing inflammatory disease in mammalian patient in need of such treatment comprising ad¬ ministering to said mammalian patient an effective amount of a propenone compound represented by general chemical formula (I) or (Ia), together with a pharmaceutically acceptable carrier thereof. [85] [86] The present compound did not show any acute toxicity when it is administrated orally to mice at the dose of 1000mg/kg and any adverse action in organ function including liver therefore it can be safely administrated into patient for long term period to prevent various inflammatory disease. [87] [88] It will be apparent to those skilled in the art that various modifications and variations can be made in the compositions, use and preparations of the present invention without departing from the spirit or scope of the invention. [89] [90] The present invention is more specifically explained by the following figures and examples. However, it should be understood that the present invention is not limited to these examples in any manner. [91] Advantageous Effects [92] The novel propenone compound of the present inventionshows a potent anti¬ inflammatory activity confirmed by various experiments and it can be useful in treating and preventing various inflammatory diseases. Brief Description of the Drawings [93] The above and other objects, features and other advantages of the present invention will more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which; [94] [95] Fig. 1 presents the effect of FPP-3 on the COX-2 protein expression and PGD production in BMMC (bone marrow derived mast cells); [96] Fig. 2 presents the effect of FPP-3 on the LTC 4 production by 5-LOX in BMMC; [97] Fig. 3 presents the inhibitory effect of propenone derivatives of the present invention on the NO production; [98] Fig. 4 represents the effect of FPP-3 on the iNOS protein expression and BNO production in BMMC; [99] Fig. 5 shows the cytoxicity of FPP-3; [100] Fig. 6 presents the effect of FPP-3 on LPS induced TNF-alpha production in Raw 264.7 cell; [101] Fig. 7 represents the effect of FPP-3 on LPS induced IL 1-beta production in Raw 264.7 cell; [102] Fig. 8 presents the effect of FPP-3 on LPS induced I kappa B-alpha reduction in Raw 264; [103] Fig. 9 represents the effect of FPP-3 on tyrosine kinase activity in Raw 264; [104] Fig. 10 shows the effect of FPP-3 on NF-kappa B transcription in Raw 264; [105] Fig. 11 presents the effect of FPP-3 on the COX-2 protein expression and PGE production in Raw 264. Best Mode for Carrying Out the Invention [106] It will be apparent to these skilled in the art that various modification and variation can be made in the compositions, use and preparations of the present invention without departing from the spirit or scope of the invention, the present invention is more specifically explained by the following eamples, However, it should be understood that the present invention is not limited to these examples in any manner. [107] Mode for the Invention [108] Example 1. Preparation of 3-pheny-l-pyridin-2-yl-propenone (1) [109] 2.12g of 2OmM benzaldehyde was added to iced 2OmM KOH solution prepared by dissolving 1.32g of KOH in 8 ml of water and 40 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.42g of 2OmM 2-acetyl pyridine was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further pu¬ rification by Silica gel column chromatography (developing solvent EtOAc: n-hexane= 1:4, v/v) to obtain 3.2Og of yellowish green colored solid 3-phenyl-2-pyridin-2-yl-propenone (1) (Yield: 76.45%): [HO] [111] mp 74.7-75.3 0C [112] TLC R = 0.464 (EtOAc: n-hexane= 1 :2, v/v) [113] 1H-NMR (250 MHz, CDCl ): δ 8.74 (ddd, /= 4.8, 1.7, 1.0 Hz, IH, pyridine H -6), 8.31 (d, /= 16.1 Hz, IH, -CH=CH-CO-), 8.19 (dt, /= 7.8, 1.0 Hz, IH, pyridine H-3), 7.94 (d, /= 16.1 Hz, IH, -CH=CH-CO-), 7.87 (dt, /= 7.8, 1.7 Hz, IH, pyridine H-4), 7.75-7.72 (m, 2H, phenyl H-2 & H-6), 7.48 (ddd, /= 7.6, 4.8, 1.2 Hz, IH, pyridine H- 5), 7.43-7.40 (m, 3H, phenyl H-3, H-4 & H-5). [114] [115] Example 2. Preparation of 3-furan-2-yl-l-pyridin-2-yl-propenone (2) [116] l-92g of 2OmM furaldehyde was added to iced 2OmM KOH solution prepared by dissolving 1.32g of KOH in 8 ml of water and 40 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.42g of 2OmM 2-acetyl pyridine was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further pu¬ rification by Silica gel column chromatography (developing solvent EtOAc: n-hexane= 1:4, v/v) to obtain 2.92 g of yellow colored solid 3-furan-2-yl-l-pyridin-2-yl-propenone (2) (Yield: 73.3%): [117] [118] mp 51-53 0C [119] TLC R = 0.402 (EtOAc: n-hexane= 1:2, v/v) [120] 1H-NMR (250 MHz, CDCl ): δ 8.74 (ddd, /= 4.8, 1.7, 1.0 Hz, IH, pyridine H-6), 8.17 (dt, /= 7.8, 1.0 Hz, IH, pyridine H-3), 8.14 (d, /= 15.8 Hz, IH, -CH=CH-CO-), 7.87 (dt, /= 7.8, 1.7 Hz, IH, pyridine H-4), 7.70 (d, /= 15.8 Hz, IH, -CH=CH-CO-), 7.54 (d, /= 1.8 Hz, IH, furan H-5), 7.48 (ddd, /= 7.6, 4.8, 1.2 Hz, IH, pyridine H-5), 6.77 (d, /= 3.4 Hz, IH, furan H-3), 6.52 (dd, /= 3.4, 1.8 Hz, IH, furan H-4). [121] [122] Example 3. Preparation of 3-furan-3-yl-l-pyridin-2-yl-propenone (3) [123] l-92g of 2OmM furaldehyde was added to iced 4OmM KOH solution prepared by dissolving 2.64g of KOH in 10 ml of water and 70 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 4.85g of 4OmM 2-acetyl pyridine was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further pu¬ rification by Silica gel column chromatography varying the ratio of developing solvent (EtOAc: n-hexane, v/v) from 1:3 to 2:1 to obtain 7.65 g of yellow colored solid 3-furan-3-yl-l-pyridin-2-yl-propenone (3) (Yield: 96%): [124] [125] mp 74.2-75.2 0C [126] TLC Rf= 0.415 (EtOAc: n-hexane= 1:2, v/v) [127] 1H-NMR (250 MHz, CDCl ): δ 8.74 (ddd, /= 4.8, 1.7, 1.0 Hz, IH, pyridine H-6), 8.17 (dt, /= 7.9, 1.0 Hz, IH, pyridine H-3), 7.99 (d, /= 15.8 Hz, IH, -CH=CH-CO-), 7.87 (dt, /= 7.7, 1.7 Hz, IH, pyridine H-4), 7.84-7.82 (m, IH, furan H-2), 7.81 (d, /= 15.8 Hz, IH, , -CH=CH-CO-), 7.48 (ddd, /= 7.6, 4.8, 1.2 Hz, IH, pyridine H-5), 7.47-7.46 (m, IH, furan H-5), 6.81 (dd, /= 1.3, 0.6 Hz, IH, furan H-4). [128] [129] Example 4. Preparation of 3-pyridin-2-yl-3-thiophen-2-yl-propenone (4) [130] 1.92g of 2OmM 2-thiophene carboxaldehyde was added to iced 2OmM KOH solution prepared by dissolving 1.32g of KOH in 8 ml of water and 40 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.42g of 2OmM 2-acetyl pyridine was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further purification by Silica gel column chromatography (developing solvent EtOAc: n-hexane= 1:4, v/v) to obtain 3.83 g of yellow colored solid 3-pyridin-2-yl-3-thiophen-2-yl-propenone (4) (Yield: 89%): [131] [132] mp 75.2-75.8 0C [133] TLC R = 0.44 (EtOAc: n-hexane= 1:2, v/v) [134] 1H-NMR (250 MHz, CDCl ): δ 8.75 (ddd, /= 4.8, 1.7, 0.9 Hz, IH, pyridine H-6), 8.18 (dt, /= 7.7, 1.1 Hz, IH, pyridine H-3), 8.07 (d, /= 0.4 Hz, 2H, -CH=CH-), 7.87 (dt, /= 7.7, 1.7 Hz, IH, pyridine H-4), 7.48 (ddd, /= 7.7, 4.8, 1.2Hz, IH, pyridine H-5), 7.44 (dd, /= 5.0, 1.1 Hz, IH, thiophene H-5), 7.42 (dd, /= 3.7, 1.1 Hz, IH, thiophene H-3), 7.09 (dd, /= 5.0, 3.7 Hz, IH, thiophene H-4). [135] [136] Example 5. Preparation of l-pyridin-2-yl-3-thiophen-3-yl-propenone (5) [137] 2.24g of 2OmM 3-thiophene carboxaldehyde was added to iced 2OmM KOH solution prepared by dissolving 1.32g of KOH in 8 ml of water and 40 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.42g of 2OmM 2-acetyl pyridine was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further purification by Silica gel column chromatography (developing solvent EtOAc: n-hexane= 1:4, v/v) to obtain 3.06 g of pale yellow colored solid l-pyridin-2-yl-3-thiophen-3-yl-propenone (5) (Yield: 71%): [138] [139] mp 75.2-75.8 0C [140] TLC Rf= 0.44 (EtOAc: n-hexane= 1 :2, v/v) [141] 1H-NMR (250 MHz, CDCl ): δ 8.75 (ddd, /= 4.8, 1.7, 0.9 Hz, IH, pyridine H-6), 8.18 (dt, /= 7.7, 1.1 Hz, IH, pyridine H-3), 8.07 (d, /= 0.4 Hz, 2H, -CH=CH-), 7.87 (dt, /= 7.7, 1.7 Hz, IH, pyridine H-4), 7.48 (ddd, /= 7.7, 4.8, 1.2Hz, IH, pyridine H-5), 7.44 (dd, /= 5.0, 1.1 Hz, IH, thiophene H-5), 7.42 (dd, /= 3.7, 1.1 Hz, IH, thiophene H-3), 7.09 (dd, /= 5.0, 3.7 Hz, IH, thiophene H-4). [142] [143] Example 6. Preparation of 3-furan-2-yl-l-pyridin-3-yl-propenone (6) [144] l-32g of 2OmM 2-furaldehyde was added to iced 4OmM KOH solution prepared by dissolving 1.32g of KOH in 8 ml of water and 40 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.42g of 2OmM 3-acetyl pyridine was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further pu¬ rification by Silica gel column chromatography varying the ratio of developing solvent (EtOAc: n-hexane, v/v) from 1:2 to obtain 2.23 g of orange colored solid 3-furan-2-yl-l-pyridin-3-yl-propenone (6) (Yield: 56.0%): [145] [146] mp 84.2-84.7 0C [147] TLC R = 0.184 (EtOAc: n-hexane= 1:2, v/v) [148] 1H-NMR (250 MHz, CDCl ): δ 9.24 (dd, /= 2.2, 0.7 Hz, IH, pyridine H-2), 8.80 (dd, /= 4.8, 1.7 Hz, IH, pyridine H-6), 8.30 (dt, /= 8.0, 2.0 Hz, IH, pyridine H-4), 7.64 (d, /= 15.3 Hz, IH, -CH=CH-CO-), 7.56 (d, /= 1.8 Hz, IH, , furan H-5), 7.46 (ddd, /= 8.0, 4.9, 0.8 Hz, IH, pyridine H-5), 7.42 (d, /= 15.3 Hz, IH, -CH=CH-CO-), 6.78 (d, / = 3.4 Hz, IH, furan H-3), 6.54 (dd, /= 3.4, 1.8 Hz, IH, furan H-4). [149] [150] Example 7. Preparation of 3-furan-3-yl-l-pyridin-3-yl-propenone (7) [151] l-32g of 2OmM 3-acetyl pyridine was added to iced 4OmM KOH solution prepared by dissolving 1.32g of KOH in 8 ml of water and 40 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.42g of 2OmM 3-acetyl pyridine was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further pu¬ rification by Silica gel column chromatography (developing solvent, EtOAc: n- hexane= 1 :2, v/v) to obtain 2.43 g of yellow colored solid 3-furan-3-yl-l-pyridin-3-yl-propenone (7) (Yield: 61.0%): [152] [153] mp 95.2-95.7 0C [154] TLC R = 0.15 (EtOAc: n-hexane= 1:2, v/v) [155] 1H-NMR (250 MHz, CDCl ): δ 9.20 (dd, /= 2.2, 0.7 Hz, IH, pyridine H-2), 8.80 (dd, /= 4.8, 1.7 Hz, IH, pyridine H-6), 8.30 (dt, /= 8.0, 2.0 Hz, IH, pyridine H-4), 7.80-7.78 (m, IH, furan H-2), 7.77 (d, /= 15.4 Hz, IH, -CH=CH-CO-), 7.51-7.49 (m, IH, , furan H-5), 7.45 (ddd, /= 8.0, 4.9, 0.8 Hz, IH, pyridine H-5), 7.21 (d, /= 15.4 Hz, IH, -CH=CH-CO-), 6.73 (dd, /= 1.3, 0.6 Hz, IH, furan H-4). [156] [157] [158] Example 8. Preparation of l-pyridin-3-yl-3-thiophen-3-yl-propenone (8) [159] 2.24g of 2OmM 3-thiophene carboxaldehyde was added to iced 2OmM KOH solution prepared by dissolving 1.32g of KOH in 8 ml of water and 40 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.42g of 2OmM 3-acetyl pyridine was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further purification by Silica gel column chromatography (developing solvent, EtOAc: n-hexane= 1:2, v/v) to obtain 2.6 g of yellow colored solid l-pyridin-3-yl-3-thiophene-3-yl-propenone (8) (Yield: 60.5%): [160] [161] mp 90.6-91.0 0C [162] TLC Rf= 0.16 (EtOAc: n-hexane= 1:2, v/v) [163] 1H-NMR (250 MHz, CDCl ): δ 9.21 (dd, /= 2.2, 0.7 Hz, IH, pyridine H-2), 8.80 (dd, /= 4.8, 1.7 Hz, IH, pyridine H-6), 8.28 (dt, /= 8.0, 2.0 Hz, IH, pyridine H-4), 7.84 (d, /= 15.5 Hz, IH, -CH=CH-CO-), 7.66 (m, IH, thiophene H-2), 7.46 (ddd, /= 8.0, 4.9, 0.8 Hz, IH, pyridine H-5), 7.45-7.43 (m, 2H, thiophene H-4 & H-5), 7.31 (d, /= 15.5 Hz, IH, -CH=CH-CO-). [164] [165] Example 9. Preparation of 1,3-diphenyl-propenone (9) [166] 2.03ml of 2OmM benzaldehyde was added to iced 2OmM KOH solution prepared by dissolving 1.32g of KOH in 5 ml of water and 30 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.33ml of 2OmM acetophenone was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and dried with vaccuo to obtain 4.1 g of pale green colored needle 1,3-diphenyl propenone (9) (Yield: 98.4%): [167] [168] mp 57.0-58.7 0C [169] TLC R = 0.30 (EtOAc: n-hexane= 1:5, v/v) [170] 1H-NMR (250 MHz, CDCl ): δ 8.04-8.01 (m, 2H, 1-phenyl H-2, H-6), 7.82 (d, /= 15.7 Hz, IH, -CH=CH-CO-), 7.66-7.63 (m, 2H, 3-phenyl H-2 & H-6), 7.60-7.47 (m, 3H, 3-phenyl H-3, H-4, H-5), 7.53 (d, /= 15.7 Hz, IH, -CH=CH-CO-). 7.43-7.40 (m, 3H, 1-phenyl H-3, H-4, H-5). [171] [172] [173] Example 10. Preparation of l-phenyl-3-thiophen-2-yl-propenone (10) [174] 1.87 ml of 2OmM 2-benzaldehyde was added to iced 2OmM 85% KOH solution prepared by dissolving 1.32g of KOH in 5 ml of water and 30 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.33ml of 2OmM acetophene was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and dried with vaccuo to obtain 4.2 g of pale yellowish green colored needle l-pheny-3-thiophen-2-yl-propenone (10) (Yield: 98.4%): [175] [176] mp 58.1-59.8 0C [177] TLC R = 0.30 (EtOAc: n-hexane= 1:5, v/v) [178] 1H-NMR (250 MHz, CDCl ): δ 8.03-7.99 (m, 2H, phenyl H-2, H-6), 7.95 (d, /= 15.5 Hz, IH, -CH=CH-CO-), 7.61-7.47 (m, 3H, phenyl H-3, H-4, H-6), 7.42 (d, , /= 5.0 Hz, IH, thiophene H-3), 7.36 (d, /= 3.7 Hz, IH, thiophene H-5), 7.34 (d, /= 15.5 Hz, IH, -CH=CH-CO-), 7.09 (dd, /= 5.0, 3.7 Hz, IH, thiophene H-4). [179] [180] [181] Example 11. Preparation of l,3-di-thiophen-2-yl-propenone (11) [182] 1.87 ml of 2OmM 2-benzaldehyde was added to iced 2OmM 85% KOH solution prepared by dissolving 1.32g of KOH in 5 ml of water and 30 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.33ml of 2OmM acetophene was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and dried with vaccuo to obtain 4.2 g of pale yellowish green colored needle l-pheny-3-thiophen-2-yl-propenone (11) (Yield: 98.4%): [183] [184] mp 58.1-59.8 0C [185] TLC R = 0.30 (EtOAc: n-hexane= 1:5, v/v) [186] 1H-NMR (250 MHz, CDCl ): δ 8.03-7.99 (m, 2H, phenyl H-2, H-6), 7.95 (d, /= 15.5 Hz, IH, -CH=CH-CO-), 7.61-7.47 (m, 3H, phenyl H-3, H-4, H-6), 7.42 (d, , /= 5.0 Hz, IH, thiophene H-3), 7.36 (d, /= 3.7 Hz, IH, thiophene H-5), 7.34 (d, /= 15.5 Hz, IH, -CH=CH-CO-), 7.09 (dd, /= 5.0, 3.7 Hz, IH, thiophene H-4). [187] [188] Example 12. Preparation of l,3-thiophen-3-yl-l-thiophen-2-yl-propenone (12) [189] 1.85 ml of 2OmM 2-benzaldehyde was added to iced 2OmM 85% KOH solution prepared by dissolving 1.32g of KOH in 5 ml of water and 30 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.16ml of 2OmM 2-acetyl thiophene was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and dried with vaccuo to obtain 3.72 g of yellowish green colored needle 3-thiophen-3-yl-l-thiophen-2-yl-propenone (12) (Yield: 84.4%): [190] [191] TLC R = 0.20 (EtOAc: n-hexane= 1:5, v/v) [192] 1H-NMR (250 MHz, CDCl ): δ 7.85, (d, /= 3.8Hz, 1 H, 1-thiophene H-5), 7.84 (d, / = 15.4Hz, 1 H, -CH=CH-CO-), 7.67 (d, /= 4.9Hz, 1 H, 1-thiophene H-3), 7.62 (d, / = 1.5Hz, 1 H, 3-thiophene H-2), 7.43-7.36 (m, 2 H, 3-thiophene H-4, H-5), 7.24 (d, / = 15.4Hz, 1 H, -CH=CH-CO-), 7.18 (dd, /= 4.9, 3.8Hz, 1 H, 1-thiophene H-4) [193] [194] Example 13. Preparation of 3-furan-2-yl-l-thiophen-2-yl-propenone (13) [195] 1.66 ml of 2OmM 2-benzaldehyde was added to iced 2OmM 85% KOH solution prepared by dissolving 1.32g of KOH in 5 ml of water and 30 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 2.16ml of 2OmM 2-acetyl thiophene was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and dried with vaccuo to obtain 3.95 g of yellow colored needle 3-furan-2-yl-l-thiophen-2-yl-propenone (13) (Yield: 96.7%): [196] [197] mp 68.4-69.9 0C [198] TLC R = 0.20 (EtOAc: n-hexane= 1:5, v/v) [199] 1H-NMR (250 MHz, CDCl ): 7.86 (dd, /= 3.8, 1.1Hz, 1 H, thiophene H-5), 7.68 (dd, / = 4.9, 1.1Hz, 1 H, thiophene H-3), 7.61 (d, / = 15.3Hz, 1 H, -CH=CH-CO-), 7.54 (d, / = 1.8Hz, 1 H, furan H-5), 7.33 (d, / = 15.3Hz, 1 H, -CH=CH-CO-), 7.18 (d, / = 4.9, 3.8Hz, 1 H, thiophene H-4), 6.73 (d, /= 3.4Hz, 1 H, furan H-3), 6.52 (dd, / = 3.4Hz, 1.8Hz, 1 H, furan H-4) [200] [201] Example 14. Preparation of l,3-di-furan-2-yl-propenone (14) [202] 3.32 ml of 4OmM 2-benzaldehyde was added to iced 4OmM 85% KOH solution prepared by dissolving 2.64g of KOH in 10 ml of water and 60 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 4.0ml of 4OmM 2-acetyl furan was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further purification by Silica gel column chromatography (developing solvent, EtOAc: n- hexane= 1:4, v/v) to obtain 6.41 g of pale yellow colored needle l,3-di-furan-2-yl-propenone (14) (Yield: 85.4%): [203] [204] mp 88.2-89.6 0C [205] TLC Rf= 0.39 (EtOAc: n-hexane= 1 :2, v/v) [206] 1H-NMR (250 MHz, CDCl : 7.65 (dd, /= 1.7Hz, 0.7Hz, IH, 1-furan H4 ) 7.63 ( d, / = 15.4Hz, IH, -CH=CH-CO- ) 7.53 ( d, / = 1.7Hz, IH, 3-furan H4 ) 7.32 ( dd, / = 3.6Hz, 0.7Hz, IH, 1-furan H2 ) 7.31 ( d, / = 15.4Hz, 2H, -CH=CH-CO- ) 6.73 ( d, / = 3.4, 3-furan H2) 6.59 ( dd, /= 3.6Hz, 1.7Hz, IH, 1-furan H3 ) 6.52 ( dd, / = 3.4Hz, 1.7Hz, IH, 3-furan H3 ) [207] [208] Example 15. Preparation of l-furan-2-yl-3-pyridin-2-yl-propenone (15) [209] 5.2 ml of 54.85mM 2-pyridinecarboxaldehyde was added to NaOH solution prepared by dissolving 34g of NaOH in EtOH and was allowed to reaction at 25°C in nitrogen atmosphere. After 10 minutes, 5ml of 49.86mM 2-acetyl furan was added thereto and stirred at 25°C for 3 hours. 80ml of water was added to the mixture solution and organic layer was extracted with 120ml of CH Cl . The organic layer was washed with 80ml of water twice and 80ml of saturated NaCl solvent and dried with Na SO . 2 4 Remaining solvent was removed and the residue was subjected to further purification by Silica gel column chromatography (developing solvent, EtOAc: n-hexane= 1:2, v/v) to obtain 3.48 g of yellow colored crystal of l-furan-2-yl-3-pyridin-2-yl-propenone (15) (Yield: 38.7%): [210] [211] [212] TLC R = 0.167 (EtOAc: n-hexane= 1:2, v/v) [213] 1H-NMR (250 MHz, CDCl : 8.70 (ddd, /= 4.8, 1.7, 0.9Hz, 1 H, pyridin H-6), 7.97 (d, / = 15.4Hz, 1 H, -CH=CH-CO), 7.84 (d, /= 15.4Hz, 1 H, -CH=CH-CO-), 7.75 (dt, / = 7.7, 1.8Hz, 1 H, pyridine H-4), 7.68 (dd, / = 1.7, 0.7Hz, 1 H, pyridine H-5), 7.48 (dt, / = 7.8, 1.2Hz, 1 H, pyridine H-3), 7.42 (dd, /= 3.6, 0.7Hz, 1 H, furan H-3), 7.31 (ddd, / = 7.6, 4.8, 1.1Hz, 1 H, pyridine H-5), 6.61 (dd, / = 3.6, 1.7Hz, 1 H, furan H-4) [214] [215] Example 16. Preparation of 3-(3-methyl-thiophen-2-yl)-l-pyridin-2-yl-propenone (16) [216] 3.85 ml of 35.66mM 3-methyl-2-thiophene-carboxaldehyde was added to iced 35.66mM 85% KOH solution prepared by dissolving 2.35g of KOH in 10 ml of water and 60 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 4.0ml of 35.66mM 2-acetyl pyridine was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further purification by Silica gel column chromatography (developing solvent, EtOAc: n-hexane= 1:3, v/v) to obtain 6.43g of green color of 3-(3-methyl-l-thiophen-2-yl)-l-pyridin-2-yl-propenone (16) (Yield: 78.6%): [217] [218] mp 100.1-111.6 0C [219] TLC R = 0.60 (EtOAc: n-hexane= 1:2, v/v) [220] 1H-NMR (250 MHz, CDCl : 8.74 (ddd, / = 4.8, 1.7, 0.9Hz, 1 H, pyridine H-6), 8.18 (dt, / = 8.0, 1.0Hz, 1 H, pyridine H-3), 8.15 (d, /= 15.7Hz, 1 H, -CH=CH-CO-), 8.02 (d, / = 15.6Hz, 1 H, -CH=CH-CO-), 7.87 (dt, /= 7.7, 1.7Hz, 1 H, pyridine H-4), 7.48 (ddd, / = 7.5, 4.8, 1.2Hz, 1 H, pyridine H-5), 7.33 (d, / = 5.1Hz, 1 H, thiophene H-5), 6.91 (d, / = 5.1Hz, 1 H, thiophene H-4) [221] [222] Example 17. Preparation of l-(5-chloro-thiophen-2-yl)-3-furan-2-yl-propenone (17) [223] 2.10 ml of 24.9mM 2-furaldehyde was added to iced 24.9mM 85% KOH solution prepared by dissolving 1.64g of KOH in 7 ml of water and 40 ml of MeOH. The solution was allowed to reaction. After 10 minutes, 4.Og of 24.9 mM 2-acetyl 5-chlorothiophene was added thereto, stirred in ice bath for 3 hours and subjected to filtration to obtain their residue. The residue was washed with 40 mM cold methanol and subjected to further purification by Silica gel column chromatography (developing solvent, EtOAc: n-hexane= 1:10, v/v) to obtain 5.47 g of yellow colored 3-(5-chloro-thiophen-2-yl)-3-furna-2-yl-propenone (17) (Yield: 92%): [224] [225] mp 85.5-87.0 0C [226] TLC R = 0.41 (EtOAc: n-hexane= 1 :5, v/v) [227] 1H-NMR (250 MHz, CDCl : 7.63 (d, / = 4. IHz, 1 H, thiophene H-3), 7.59 (d, / = 15.3Hz, 1 H, -CH=CH-CO-), 7.54 (d, /= 1.3Hz, 1 H, furan H-5), 7.23 (d, / = 15.2Hz, 1 H, -CH=CH-CO-), 7.00 (d, / = 4.1Hz, 1 H, thiophene H-3), 6.74 (d, / = 3.4Hz, 1 H, furan H-3), 6.53 (dd, / = 3.4, 1.8Hz, 1 H, furan H-4) [228] [229] Reference Example 1. Preparation [230] [231] Experimental material and reagent [232] Balb/c male mouse was purchase from Hyochang Science (Seoul, Korea) and RAW 264.7 cell, a rodent macrophage, was from ATCC (American Type Culture Collection). l-Palmitoyl-2-[l- C]-arachidonyl-phosphatidyl ethanol amine) was purchase from NEN Co, [3H] -acetyl coenzyme A from Amersham Biosciences Co., and n-heptane from Yakuri Pure Chemical Co. Acetyl Coenzyme A, BSA (Bovine Serum album), aspirin, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide), N-(l-naphthyl)ethylenediamine were purchased from Sigma Chemical Co. Recombinant mouse c-kit ligand (KL) was prepared by YoungNam University and Bradford protein assay reagent was purchased from BIO-RAD Co. PGDl and LTC4 Enzyme linked immunoassay (EIA) kit was purchased from Cayman Chemical Co., TNF-alpha and IL 1-beta ELISA kit from R&D Co., and PDE enzyme linked im¬ munoassay kit from Amersham Biosciences Co., RPMI- 1640, lipopectamine 2000, Opti-MEM were purchased from GIBCO BRL Co., and FBS from JBI Co. DMSO was purchase from Merck Co., POPOP(1, 4-bis[2-phenyoxazolyl] -benzene and DPO (2,5-diphenyl-oxazole) from Dojin Co., and MeOH, EtOH and Isopropanol were from Cayman Chemical Co. Chloroform was purchased from Junsei Co. and iNOS antibody and I kappa B alpha were purchased from Santa-Cruz Co. COX-2 antibody was purchased from Cayman Chemical Co and PERK and PP38 antibodies were from Cell Signaling Co. [233] [234] Experimental Analysis [235] To determine the structure of synthetic materials, H-NMR and C-NMR (Bruker AMX 250 model)were used in this experiment. Finnigan LCQ Advantage was used as a LC/Mass Spectrometry and the data obtained from LC/MS spectrometry was analyzed by Xcalibur program. Kieselgel 60 F 254 and Silicagel Kieselgel 60 (240-400 mesh) purchased from Merck Co. were used in TLC (Thin layer chromatography) and column chromatography. SPD MlOA Diode system purchased from Shimadzu Co.(Japan) was used to analyze the identification and qualitative determination of molecular as a HPLC. [236] [237] Cell culture [238] [239] The bone marrow cells collected from Balb/c male mouse was added to RPMI 1640 culture medium containing 10% FBS, 100 U/ml penicillin, 100u/ml of streptomycin and 100 uM MEM non-essential amino acid to the extent the final con¬ centration of IL-3 (the supernatant of mouse spleen cells) to 10ng/ml and incubated for about three weeks to obtain BMMC (Bone Marrow-derived mast cell) having more than 90% of homogenicity. RAW 264.7 cell was incubated in RPMI 1640 medium containing 10% FBS, 100 U/ml penicillin and 100 mg/ml of streptomycin. The cell was incubated in 5% CO incubator at 37 0C and incubated cells were divided into 2 6-wells or 12-wells and several numbers of cells were divided into 96-cells in case of BMMC culture. [240] [241] Experimental Example 1. Effect on the various enzymes involved in arachidonic acid metabolic system [242] [243] 1-1. lyso PAF- acetyltransf erase actvity [244] In order to confirm the inhibitory effect of the present compounds obtained in above the Examples on lyso PAF-acetyltransferase activity, the experiment was performed with the procedure described in the literature (Yanoshita R. et al., In¬ flammation Res., 45, p546, 1996). [245] [246] lOuM lyso PAF and 20OuM [3H] -acetyl coenzyme A were used as substrates. The mass incubated and homogenized RBL-2H3 cell lines derived from rat basophilic leukocyte were subjected to centrifugation (100000xg) using by pellet and the cells were added to 10OmM final concentration of Tris-HCl (pH 6.9). Various con¬ centrations of propenone compounds were added thereto and allowed to reaction at 37°C for 10 minutes. The reaction was stopped by adding 1.5 ml of solvent mixture mixed with chloroform and MeOH (1:2) and 30ul of acetic acid, and appropriate amount of CHCl and MeOH was added and centrifuged to obtain organic layer. The formed [ H]-PAF from organic layer determined by Liquid Scintillation Counter (LSC, Beckman, Germany). [247] [248] 1-2. PLA -inhibition actvitv [249] In order to confirm the inhibitory effect of the present compounds obtained in above the Examples on PLA activity, the experiment was performed with following procedure. [250] [251] Appropriate amount of l-Palmitoyl-2-[l- 14 C, ]-arachidonyl-phosphatidyl ethanol amine (NEN Co.) was added to test tube. Solvent free substrate film by nitrogen gas was treated with appropriate amount of distilled water and subjected to ultra- sonication treatment (Branson 2200, USA) to use as a substrate. The reaction mixture containing 4mM CaCl , 10OmM Tris-HCl (pH 9), 0.3mM substrate, enzyme and various con¬ centration test sample was reacted at 37°C for a time and the reaction was stopped by adding Dole s reagent. The solution was centrifuged and remaining lyso-complex was removed by Silica gel and the amount of released [ C]-arachidonic acid was determined to transform into PLA activity. [252] [253] 1-3. Result [254] As can be seen in following Table 1, most of test compounds did not show significant activities at the result of determining the activity of lyso PAF-acetyl transferase enzyme (final concentration, 50ug/ml), a rate determining enzyme in PAF synthesis, and the activity of sPLA2 HA (final concentration 2.5ug/ml) through de¬ termining the amount of beta-hexosimidase (final concentration 25ug/ml), which are closely correlated with inflammatory and allergic disease directly or indirectly. [255] Table 1

[256] [257] Experimental Example 2. Effect on PGD reproduction caused by COX-I and COX-2 [258] [259] 2-1. PGD formation assay 2. [260] In order to confirm the inhibitory effect of the present compounds obtained in above the Examples on PGD2 reproduction caused by COX-I and COX-2, the experiment was performed with following procedure. [261] [262] 100 ng/ml KL (c-kit ligand) used as a stimulator, 100 U/ml of IL-10 and 100 ng/ml of LPS were treated with Ix 10 cells/ml concentration of BMMC. Various con¬ centrations of propenone compounds were treated therewith and the cells were incubated at 37°C for 8 hours in 5% CO 2 atmosphere condition to determine the re- producing amount of PGD for determining COX-2 activity. The COX-I enzyme activity was inactivated by treating COX enzymes with lOug/ml of aspirin factor prior to the reaction. The test samples were pretreated before the reaction in the final con¬ centration of 12.5 ug/ml). After stopping the reaction, the solution was centrifuged (120xg, 4°C for 5 mins) and the PGD reproducing amount in supernatant was determined using by PGD assay kit (Cayman Co.). [263] [264] 2-2. Result of PGD reproduction caused by COX- 1 and 2 2_ — [265] As can be seen in following Table 2 and 3, most of test compounds show potent inhibitory effect on the activity of COX-2 enzyme whereas relatively lower inhibitory effect on COX-I activity than that of COX-2. Particularly, compounds 12 and 15 (FPP-3) showed enzyme selectivity and the IC value of each compound was shown in Table 3. [266] [267] Table 2

[268]

[269] [270] 2-3. Effect of FPP-3 on the COX-2 protein expression and PGD formation 2_ [271] Further to the study of above 2-1 and 2-2 experiments, FPP-3 was treated with COX-I inactivated BMMC with aspirin pretreatment (lOug/ml) and the cell was activated with KL, LPS and IL-IO for 8 hours to determine their protein expression. At the result of determining the PGD2 amount in the supernatant using by EIA kit, it is confirmed that FPP-3 inhibited COX-2 protein expression and PGD2 reproduction in a dose dependent manner and showed 28.1 uM of IC value (See Fig.1). [272] To observe the protein expression of the cells, Western Blot method was used and COX-2 isolated through electrophoresis was transferred to nitrocellulose membrane using by buffer solution containing 20% MeOH, 25mM Tris and 192mM glycine. Ponceau solution was used to confirm whether the protein of membrane was moved or not and the reaction was blocked by reacting with 5% skim- milk solution at R. T. for 30 mins. Primary antibody diluted with blocking buffer solution and the membrane was further allowed to reaction for more than 4 hours. After stopping the reaction, the solution was washed with TTBS (Tris-Tween buffer saline) six times at every five minutes intervals, reacted with secondary antibody attached with HRP (Horse Radish Peroxidase), washed again with TTBS and distilled water six times. After washing, the solution was reacted with ECL solution for 2 minutes and the width of exposed band was compared to confirm whether the protein was expressed or not and the expression difference (See Fig.l). [273] [274] Experimental Example 3. Effect on LTC reproduction caused by 5-LOX [275] [276] 3-1. LTC formation assay 4. [277] [278] Various concentrations of propenone compounds were added to Ix 10 cells/ml concentration of BMMC and the cell was pre-incubated at 37 0C for 30 minutes in 5% CO atmosphere condition. 100 ng/ml KL (c-kit ligand) was added to thereto and the cell was incubated at 37 0C for 20 minutes in 5% CO atmosphere condition. The cell was centrifuged and the supernatant was collected to determine the LTC amount in the 4 supernatant using by LTC 4 assay kit (Cayman Co.). [279] [280] 3-2. The effect of propenone compounds on LTC reproduction caused by 5-LOX [281] [282] According to the procedure disclosed in Experimental Example 3-1, BMMC was activated with KL and the inhibitory effect of various concentrations of propenone compounds (final cone: 25 ug/ml) on the 5-LOX activity present in macrophage was determined. As can be seen in Table 4, most of compounds showed potent inhibitory activities. [283] [284] 3-3. The effect of FPP- 3 compound on LTC reproduction caused by 5-LOX [285] [286] Further to Experimental Example 3-2, BMMC was activated with KL and the inhibitory effect of various concentrations of FPP-3 compounds on the 5-LOX activity present in macrophage was determined. As can be seen in Table 4, FPP-3 compound showed most potent inhibitory activities in dose dependent manner (IC = 1.6 uM). [287] Table 4

[288] a: positive control for 5-LOX (Yoshimoto, T. et al., Biochim. Biophys. Acta., 713(2) , pP470-473, 1982) [289] [290] Experimental Example 4. Effect on NO reproduction and iNOS protein expression [291] [292] 4-1. PGE formation assay [293] [294] RAW 264.7 cells was placed onto 12- well plate by dividing into 5x10 cells re¬ spectively and stabilized for 6 hours. After FPP-3 was pretreated therewith for 30 minutes, LPS was treated for 12 hours and the amount of PGE was determined by PGE assay kit (Amersham Biosciences Co.). [295] [296] 4-2. NO reproduction assay [297] [298] To examine the effect on macrophage activation, after various concentrations of propenone compounds were pre-treated with RAW264.7 cells in the final con¬ centration of 10 ug/ml for 30 minutes, LPS was treated for 24 hours and the NO re¬ production amount was determined. At the result, it is confirmed that FPP-3 showed potent inhibitory effect on NO reproduction {See Fig.3). [299] [300] 4-3. Inhibitory effect of FPP-3 in NO reproduction in RAW264.7 cell [301] [302] The reproduced amount of NO was determined by analyzing the amount of nitrite salt in incubated supernatant. 100 ul of Griess reagent containing 1% sulfanilamide, 0.1% naphthylethylenediamine dihydrochloride and 2.5% phosphoric acid was mixed with equivalent amount of cell culture medium, reacted together for 10 minutes in the dark place and the developed absorbance was determined at 570nm using ELISA. New culture medium was used as a blank and the concentration of nitrite salt was determined by being transformed with the standard curve obtained from NaNO reaction. [303] As can be seen in Fig. 4, it is confirmed that FPP-3 reduced NO reproduction in dose dependent manner and the IC of NO was 10.1 uM. [304] [305] 4-4. Inhibitory effect of FPP-3 in iNOS protein expression in RAW264.7 cell [306] [307] To examine the effect of FPP-3 on macrophage activation, various concentrations of FPP-3, i.e., 6.25 uM, 12.5 uM, 25 uM and 50 uM of sample were pretreated with RAW264.7 cell for 30 minutes and 200 ng/ml of LPS was also treated therewith. According to the experimental procedure disclosed in Experimental Example 2-3, the expression of iNOS protein was determined by Western blot analysis and it is confirmed that FPP-3 compound reduced nitrite reproduction and iNOS expression in a dose dependent manner (See Fig. 4). [308] [309] Experimental Example 5. cell cytotoxicity test of the compounds [310] [311] 5-1. MTT assay [312] [313] Various concentrations of propenone compounds were added to Ix 10 cells/ml concentration of RAW 264.7 cells and the cell was pre-incubated for 8 hours. About 0.5 mg/ml of concentration of MTT reagent was treated thereto at 37 0C for 20 minutes in 5% CO atmosphere condition. 0.04 N-HCl/ Isopropanol was added thereto to dissolve the cells completely and the absorbance was determined at 540 nm. [314] [315] 5-2. Cell cytotoxicity test of FPP-3 [316] [317] To examine the cell cytotoxicity of 25 uM FPP-3 on RAW 264.7 macrophage, MTT assay was performed. The absorbance of control cell group and the test cell groups treated with various concentrations of FPP-3, i.e., 12.5uM, 25 uM and 50 uM of sample were determined at 540nm. At the result, it is confirmed that FPP-3 compound did not show cell cytotoxicity. Additionally, the cell cytotoxicity of FPP-3 on Balb/c mouse marrow derived macrophage cell was determined by the procedure, i.e., cell staining and counting of the stained cells. After staining control cell group and the test cell groups treated with various concentrations of FPP-3, i.e., 12.5uM, 25 uM and 50 uM of sample, the stained cells were counted. It is confirmed that FPP-3 compound did not show any cell cytotoxicity. (See Fig. 5). [318] Table 5

[319] Experimental Example 6. Effect on TNF-apha, a proinflammatory cytokine, reproduction [320] [321] 6-1. TNF- alpha formation assay [322] [323] RAW264.7 cells was placed onto 12-well plate by dividing into 5x10 cells re¬ spectively and stabilized for more than 6 hours. After FPP-3 was pretreated therewith for 30 minutes, LPS was treated for 1 hour and the amount of TNF-alpha was determined by TNF-alpha assay kit (R&D Co.). [324] [325] 6-2. Inhibitory effect of FPP-3 on TNF-alpha production [326] [327] To examine the effect of FPP-3 on TNF-alpha production induced by LPS stimulation in RAW264.7 cell, various concentrations of FPP-3, i.e., 0 uM, 6.25 uM, 12.5 uM, 17.5uM, and 25 uM of sample were pretreated with RAW264.7 cell for 30 minutes and 200 ng/ml of LPS was also treated therewith for lhour. At the result, it is confirmed that FPP-3 reduced TNF-alpha production in a dose dependent manner and the IC of FPP-3 was 48.9 uM (See Fig. 6). [328] [329] Table 6

[330] [331] Experimental Example 7. Effect on IL 1-beta, a proinflammatory cytokine, production [332] [333] 7-1. IL 1-beta formation assay [334] RAW264.7 cells was placed onto 12-well plate by dividing into 5x10 cells re¬ spectively and stabilized for more than 6 hours. After FPP-3 was pretreated therewith for 30 minutes, LPS was treated for 48 hours and the amount of IL 1-beta was determined by IL 1-beta assay kit (R&D Co.). [335] [336] 7-2. Inhibitory effect of FPP-3 on IL 1-beta production [337] [338] To examine the effect of FPP-3 on IL 1-beta reproduction induced by LPS stimulation in RAW264.7 cell, various concentrations of FPP-3, i.e., 0 uM, 12.5 uM, 25 uM, 35 uM, and 50 uM were pretreated with RAW264.7 cell for 30 minutes and 200 ng/ml of LPS was also treated therewith for 1 hour. At the result, it is confirmed that FPP-3 reduced IL 1-beta reproduction in a dose dependent manner and the IC of FPP-3 was 18.7 uM (See Fig. 7). [339] [340] Experimental Example 8. Effect on I kappa B alpha dissociation caused by LPS stimulation in RAW 264.7 cell [341] [342] 8-1. 1 kappa B alpha dissociation caused by LPS stimulation [343] [344] To examine the effect of FPP-3 on the phosphorylation of I kappa B alpha caused by LPS stimulation, the reduction of I kappa B alpha according to the treatment with LPS at each 5 min, 10 mins, 20 mins, 30 mins, 1 hour, 2 hours and 3 hours and various concentrations of FPP-3, i.e., 12.5, 25. 35, 50 uM, was determined and the result was shown in Fig. 8. Through the Western blot analysis performed by the procedure similar to those in Experimental 2-3, FPP-3 pretreatment reduced I kappa B alpha in dose dependent manner (See Fig. 8). [345] Experimental Example 9. Effect on the activity of tyrosine kinase enzymes caused by LPS stimulation in RAW 264.7 cell [346] [347] 9-1. the inhibitory effect on the activity of tyrosine kinase enzymes [348] [349] To examine the inhibitory effect of FPP-3 on the activity of tyrosine kinase enzymes caused by LPS stimulation, the effect of FPP-3 compound on pERK and pP38 protein expression, an activated form of ERK (Extracellular Regulated Kinases) which is one of cell signal transferring proteins involved in various actions such as NO re¬ production caused by LPS stimulation, the formation of various iNOS expressing in¬ flammatory protein and cytokines, was determined by Western blot analysis. At the result, it is confirmed that FPP-3 inhibits pERK phosphorylation whereas it did not inhibit pP38 phosphorylation (See Fig. 9) [350] [351] Experimental Example 10. Effect on the NF-kappa B transcription caused by LPS stimulation in RAW 264.7 cell [352] [353] 10-1. Transfection and lucif erase activity analysis [354] [355] RAW264.7 cells were placed onto 12-well plate by dividing into 5x10 cells re¬ spectively and NF-kappa B promoter DNA was transfected into the cells uscing Lipo- fectamine 2000. The transfected cells were sufficiently cultured in medium for 16 hours. FPP-3 compound was pre-treated for 30 minutes and LPS was treated for 24 hours. The cells were collected, washed once, dissolved in report lysis buffer, and reacted with luciferase analytical substrate to determine the activity of luciferase by Iu- minometer. [356] [357] 10-2. The effect on NF-kappa B transcription caused by LPS stimulation in RAW 264.7 cell [358] [359] To examine the effect of FPP-3 on the NF-kappa B transcription activity caused by LPS stimulation in RAW 264.7 cell, following lucifrase assay was performed. NF- kappa B promoter DNA attached with luciferase was obtained to induce RAW 264.7 cell to temporary transformation expression. FPP-3 was pre-treated therewith and LPS was treated to isolate cell lysate. The activity of luciferase was determined and it is confirmed that the activity of FPP-3 compound was inhibited in dose dependent manner (See Fig. 10). [360] [361] Experimental Example 11. Effect on COX-2 protein expression and PGE re¬ production [362] [363] 11-1. COX-2 protein expression and PGE reproduction [364] RAW264.7 cells was stabilized for more than 6 hours, various concentrations of FPP-3, i.e., 12.5 uM, 25 uM, 35 uM, and 50 uM were pretreated with RAW264.7 cell and 200 ng/ml of LPS was also treated therewith for 12 hours. The COX-2 protein expression was observed through Western blot analysis in a similar procedure disclosed in Experimental Example 2-3. The amount of PGE in the supernatant was determined by PGE assay kit. At the result, it is confirmed that FPP-3 inhibit COX-2 protein expression and PGE reproduction in a dose dependent manner and the IC of FPP-3 was 33.7 uM (See Fig. 11). [365] RAW264.7 cells were placed onto 12-well plate by dividing into 5x10 cells re¬ spectively and NF-kappa B promoter DNA was transfected into the cells uscing Lipo- fectamine 2000. The transfected cells were sufficiently cultured in medium for 16 hours. FPP-3 compound was stabilized for more than 6 hours. After FPP-3 was pretreated therewith. [366] To examine the inhibitory effect of FPP-3 on the activity of tyrosine kinase enzymes caused by LPS stimulation, the effect of FPP-3 compound on pERK and pP38 protein expression, an activated form of ERK (Extracellular Regulated Kinases) which is one of cell signal transferring proteins involved in various actions such as NO re¬ production caused by LPS stimulation, the formation of various iNOS expressing in¬ flammatory protein and cytokines, was determined by Western blot analysis. At the result, it is confirmed that FPP-3 inhibits pERK phosphorylation whereas it did not inhibit pP38 phosphorylation (See Fig. 9). [367] [368] 11-2. Inhibitory effect of FPP-3 on IL 1-beta reproduction [369] To examine the effect of FPP-3 on IL 1-beta reproduction induced by LPS stimulation in RAW264.7 cell, various concentrations of FPP-3, i.e., 0 uM, 12.5 uM, 25 uM, 35 uM, and 50 uM were pretreated with RAW264.7 cell for 30 minutes and 200 ng/ml of LPS was also treated therewith for 1 hour. At the result, it is confirmed that FPP-3 reduced IL 1-beta reproduction in a dose dependent manner and the IC of FPP-3 was 18.7 uM (See Fig. 7). [370] [371] Experimental Example 12. Acetic acid- induced writhing test [372] [373] The acetic acid-induced writhing test for testing the analgesic activity of inventive compounds prepared from above Examples was performed by the procedure described in the literature (Lee, J. W., Bioorganic & Medicinal Chemistry, ppl713-1720, 2001). [374] Male ICR mice having its mean body weight of 25g (CDOl; Biogenomics Co. Korea) were reared in lighting controlled environment (12hrs on,12hrs off) maintaining with temperatures at 22 +2°C and the humidity at 50 +5°C and allowed to eat a diet and to drink tap water ad lib. [375] Mice were fasted overnight prior to testing and adopted to the environment. Acetic acid solution (0.7%) was administrated in the mice intraperitoneally with 5 ml/Kg body weight then the mice were put into the transparent acryl box (15x15x15 cm). 5 minutes later, the number of abdominal constrictions was counted for 10 minutes. Each group consisting of six mice was pretreated with test compounds or solvent (0.2 ml, i. p) 30 mins before the injection of acetic acid. Test compounds were dissolved in DMSO solvent. [376] [377] As can be seen in Table 7, the compound 15 of the present invention showed more potent anti-inflammatory activity than positive control, 100mg/kg of acetyl salicylic acid. [378] Table 7

[379] [380] Experimental Example 13. Acute rat paw edema test [381] [382] The acute art paw edema test for testing the anti-inflammatory activity of inventive compounds prepared from above Examples was performed by the procedure described in the literature (Carlos et al., Gen. Pharmacol., 33, pp67-71, 1999). [383] Male SPF Sprague Dawley rat (Biogenomics Co. Ltd) having its mean body weight of about 25Og were reared in lighting controlled environment (12hrs on, 12hrs off) maintaining with temperatures at 22 + 2°C and the humidity at 50 +5°C and allowed to eat a diet and to drink tap water ad lib. [384] The rats were fasted overnight prior to testing and adopted to the environment. [385] Carrageenan (1% solution) was administrated in the rats subcutaneously with 0.1 ml/mouse of complete adjuvant at the sole of its foot. The test compounds or vehicle (0.2 ml, orally) were administrated orally 30 mins before the injection of carrageenan with various dose of 1, 10 and 50 mg/kg. 20mg/kg of indomethacin was used as a positive control group. [386] [387] The edema volume increase (ml) induced by carrageen was measured by plethysmometer. [388] As can be seen in Table 8, the compound 15 of the present invention strongly inhibited the increase of rat paw edema carrageen induced rat paw edema showing more potent anti-inflammatory activity than positive control. [389] [390] Table 8

[391] [392] Experiment Example 14: Toxicity test [393] In order to examine the cytotoxicity of FPP-3, the experiment was performed as follows. [394] [395] Methods [396] The acute toxicity on SPF Sprague-Dawley rats (Biogenomics), having its mean body weight of 108.3-126.0 g, was performed using FPP-3. Each group consisting of 5 rats was administrated orally with 8000mg/kg of FPP-3 and observed for 14 days. This test was carried out in compliance with the Testing Guidelines for Safety Evaluation of Drugs (Notification No. 1999-61) issued by Korea Food and Drug Administration and the Good Laboratory Practice Regulations for Non-clinical Laboratory Studies (Notification No. 2000-63) issued by Korea Food and Drug Administration and OECD Principles of Good Laboratory Practice. [397]

[399] There were no treatment-related effects on mortality, clinical signs, body weight changes and gross findings in any group or either gender by using 8000mg/kg of FPP- 3. These results suggested that the compounds prepared in the present invention were potent and safe. [400] [401] Hereinafter, the formulating methods and kinds of excipients will be described, but the present invention is not limited to them. The representative preparation examples were described as follows. [402] [403] Preparation of injection [404] FPP-3 lOOmg [405] Sodium metabisulfite 3.0mg [406] Methyl paraben 0.8mg [407] Propyl paraben 0. lmg [408] Distilled water for injection optimum amount [409] Injection preparation was prepared by dissolving active component, controlling pH to about 7.5 and then filling all the components in 2D ample and sterilizing by con¬ ventional injection preparation method. [410] [411] Preparation of powder [412] FPP-3 500mg [413] Corn Starch lOOmg [414] Lactose lOOmg [415] Talc lOmg [416] Powder preparation was prepared by mixing above components and filling sealed package. [417] [418] Preparation of tablet [419] FPP-3 200mg [420] Corn Starch lOOmg [421] Lactose lOOmg [422] Magnesium stearate optimum amount [423] Tablet preparation was prepared by mixing above components and entabletting. [424] [425] Preparation of capsule [426] FPP-3 lOOmg [427] Lactose 50mg [428] Corn starch 50mg [429] Talc 2mg [430] Magnesium stearate optimum amount [431] Tablet preparation was prepared by mixing above components and filling gelatin capsule by conventional gelatin preparation method. [432] [433] Preparation of liquid [434] FPP-3 lOOOmg [435] Sugar 2Og [436] Polysaccharide 2Og [437] Lemon flavor 2Og [438] Liquid preparation was prepared by dissolving active component, and then filling all the components in IOOOD ample and sterilizing by conventional liquid preparation method. [439] [440] Preparation of health food [441] FPP-3 lOOOmg [442] Vitamin mixture optimum amount [443] Vitamin A acetate 70mg [444] Vitamin E l.Omg [445] Vitamin B 0.13mg [446] Vitamin B 0.15mg [447] Vitamin B6 0.5mg [448] Vitamin B 12 0.2mg [449] Vitamin C lOmg [450] Biotin lOmg [451] Amide nicotinic acid 1.7mg [452] Folic acid 50mg [453] Calcium pantothenic acid 0.5mg [454] Mineral mixture optimum amount [455] Ferrous sulfate 1.75mg [456] Zinc oxide 0.82mg [457] Magnesium carbonate 25.3mg [458] Monopotassium phosphate 15mg [459] Dicalcium phosphate 55mg [460] Potassium citrate 90mg [461] Calcium carbonate lOOmg [462] Magnesium chloride 24.8mg [463] The above mentioned vitamin and mineral mixture may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the present invention. [464] [465] Preparation of health beverage [466] FPP-3 lOOOmg [467] Citric acid lOOOmg [468] Oligosaccharide lOOg [469] Apricot concentration 2g [470] Taurine Ig [471 ] Distilled water 900D [472] Health beverage preparation was prepared by dissolving active component, mixing, stirred at 850C for 1 hour, filtered and then filling all the components in IOOOD ample and sterilizing by conventional health beverage preparation method. [473] [474] The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the present invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims. [475] Industrial Applicability [476] As described in the present invention, present invention relates to the novel propenone derivatives containing aromatic ring, a manufacturing process thereof and a composition containing the same using as an anti-inflammatory agent. The compound of the present inventionshow potent anti- inflammatory activity confirmed by various experiments for example, the inhibition test of COX and 5-LOX enzyme activity, the inhibition test of LTC reproduction and NO production, MTT assay test, the inhibition 4 test on the iNOS and COX-2 protein expression and PGE reproduction using RAW 264.7 macrophage etc. Accordingly, present compounds can be useful in treating and preventing various inflammatory diseases.